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visualization: beautiful



Bioinformatics and Genome Analysis Course. Izmir International Biomedicine and Genome Institute, Izmir, Turkey. May 2–14, 2016


art + science activism

Watch the video of this project, which features the participants who have a BRCA mutation and their interaction with the piece. The video also highlights the design and construction of the mural.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Science and art and personal stories of cancer survivors combine into this beautiful depiction of the complexity and individuality of the genome. (Free the Data)

Human Genome Art by Humans with Genomes

I recently took part in a deeply meaningful collaboration of science, art and personal stories of cancer survivors.

Together with Joanna Rudnick and Aaron De La Cruz, we sought to create a work of art that combines the science of cancer genomics and the individuals whose lives are affected by genetic mutations in the BRCA1 and BRCA2 genes, where genomic changes drastically increase one's chances of breast and ovarian cancer.

We wanted to make something that is scientifically accurate, artistically beautiful and emotionally engaging. The complexity of the genome, the multitudes of other genes and possible mutations and the millions of personal stories of hardship and survival were just a few of the elements we wanted to include the the piece.

My role was to provide the scientific direction behind the design and incorporate it into the aesthetic of Aaron De La Cruz, a street artist from San Francisco whose work echoes information, complexity, interaction and continuity. We all have a genome — a different genome. The ways in which our genomes are different is what gives us traits like hair and eye color, but is also what makes some of us predisposed to diseases like cancer.

The mural, which includes elements drawn by the cancer survivors, is part of the Free the Data campaign, which is advocating for an open access model of genome mutation databases so that scientists everywhere can analyze it and help women make informed choices about their breast-cancer risk.

The piece Importance of Data Sharing by Nature Methods illustrated the point:

Imagine you are a physician or researcher and seek to get more confirmation on the clinical impact of particular genetic variants. If your search of public databases comes up empty this does not necessarily mean that nothing is known about the mutations in question. Rather, the information may be locked away as a trade secret in a genetic testing company’s proprietary database.

The New York Times article DNA Project Aims to Make Public a Company’s Data on Cancer Genes captures the current state of the situation.

The mural was constructed on location at InVitae in San Francisco.

A video of the project is available.

Beautiful, meaningful and personal

This work will be, as far as I know, the first human annotation of mutations in the human genome by humans whose genomes have the mutations. That's quite a term!

I've always been mindful of the necessity of the mingling of art and science. In my work I tried to add things I felt about the science I thought to create work that combines our objective understanding of the world we live in with the subjective experience of living in it. This project, by far, has been the most keenly felt.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Adding emotion, keeping the science. (Free the Data)

the design

The mural was created in San Francisco on Saturday, July 13th, 2013. We are starting with a 11' x 6' wood canvas. These dimensions reflect the ratio of lengths of BRCA1 and BRCA2 proteins (1,863 and 3,418 amino acids, respectively)

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The canvas aspect ratio reflects the ratio of BRCA1 and BRCA2 protein lengths. The proteins are represented on the canvas as lines. (Free the Data)

The BRCA1 and BRCA2 proteins are drawn on the canvas as straight-line sections.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The genes are depicted on the canvas as their protein products. (Free the Data)

The locations of the participants mutations are positioned on the protein lines as circles. For individuals with large deletions, the circle is placed at the first affected amino acid. Because BRCA1 is location on the opposite strand (anti-sense), its start on the canvas is on the right.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
11 mutations, one for each of the cancer previvor and survivor participants, are placed on the protein lines as circles. The start of BRCA1 is on the right to reflect that this gene is on the anti-sense strand. (Free the Data)

The rest of the genome is now drawn. Aaron's style is perfect for depicting information and the endless complexity of the genome and its interacting elements. We were careful to include elements that indicate that the story told today is not complete. Millions of others have mutations in thousands of other genes, each potentially life-threatening. Just as the stories of our participants will continue to evolve, other stories are waiting to be told.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
BRCA1 and BRCA2 proteins and their mutations, together with the rest of the genome. Other lines and circles hint at other genes, other mutations, as well as the biochemical interactions in the cells and personal interactions of those affected by the mutations. (Free the Data)

Once the "reference" genome is depicted, participants with BRCA1 and BRCA2 mutations will complete the art work by individually marking the positions of their mutations on the art using personalized colors. With Aaron's help, everyone created their own color by mixing primary colors.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Participants fill in their mutation circles with their personalized color. (Free the Data)

From base pair, to genome, to person, to life. All it takes is one tiny change in the genome to change a life forever.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The mutations of 11 people in the vastness of the genome. What's your story? (Free the Data)

creation of free the data mural

The BRCA1 and BRCA2 lines were placed on the canvas by first pinning two pieces of string, marked with the positions of the mutations.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
String was used to mark the placing of lines and mutations. (Free the Data)

After drawing the protein lines, it was time to fill the canvas.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Over the next 4 hours, Aaron filled in the canvas with the "rest" of the genome.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Participants

Lucy, Karen, Steve, Ghecemy, Joanna, Jill, Lisa, Lynn, Ruth, Jenica, Susan

Cancer previvors and survivors who have been diagnosed with a mutation on BRCA1 or BRCA2 genes.

Joanna Rudnick (director/producer)

Joanna made her directorial debut with the Emmy-nominated In the Family, a deeply personal film about coming to terms with testing positive for the breast cancer gene BRCA1 mutation and following the storylines of other women and families facing the same hard choices. In the Family premiered at Silverdocs in 2008, was broadcast nationally on PBS P.O.V. the same year and was a finalist for the NIHCM Foundation’s Health Care Radio and Television Journalism Award.

Joanna received a master’s degree in Science and Environmental Journalism from New York University and a bachelor’s degree in English from Northwestern University. Joanna loves the opportunity to teach and mentor and served as an adjunct professor at Northwestern University’s Medill School of Journalism in the past.

She has written for several publications including Audubon Magazine, The Artful Mind, The Berkshire Record and Humanities. Before finding her way to the wonderful world of documentaries, Joanna served as an Americorps volunteer, implementing project-based environmental curricula in the San Francisco Public School System.

Joanna is one of the cancer survivors whose mutations are encoded in the art.

http://kartemquin.com/about/joanna-rudnick

Aaron De La Cruz (artist)

Aaron De La Cruz's work, though minimal and direct at first, tends to overcome barriers of separation and freely steps in and out of the realms of design, graffiti, and illustration.

The parameters he has chosen to work within actually allow him to free himself and react to the very limitations he has created. This overriding structure and the lack of deliberation while moving within creates a tension when encountering his work due to the almost computer generated grid like systems he creates by unplanned markmaking. The act and the marks themselves are very primal in nature but tend to take on distinct and sometimes higher meanings in the broad range of mediums and contexts they appear in and on.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Work by Aaron De La Cruz. (Aaron De La Cruz)

His work finds strengths in the reduction of his interests in life to minimal information. De La Cruz gains from the idea of exclusion, just because you don't literally see it doesn't mean that its not there.

http://www.aarondelacruz.com

news + thoughts

Bayesian networks

Sun 30-08-2015

This month we continue with the theme of Bayesian statistics and look at Bayesian networks, which combine network analysis with Bayesian statistics.

In a Bayesian network, nodes represent entities, such as genes, and the influence that one gene has over another is represented by a edge and probability table (or function). Bayes' Theorem is used to calculate the probability of a state for any entity.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Bayesian networks. (read)

In our previous columns about Bayesian statistics, we saw how new information (likelihood) can be incorporated into the probability model (prior) to update our belief of the state of the system (posterior). In the context of a Bayesian network, relationships called conditional dependencies can arise between nodes when information is added to the network. Using a small gene regulation network we show how these dependencies may connect nodes along different paths.

Background reading

Puga, J.L, Krzywinski, M. & Altman, N. (2015) Points of Significance: Bayesian Statistics Nature Methods 12:277-278.

Puga, J.L, Krzywinski, M. & Altman, N. (2015) Points of Significance: Bayes' Theorem Nature Methods 12:277-278.

...more about the Points of Significance column

Unentangling complex plots

Fri 10-07-2015

The Points of Significance column is on vacation this month.

Meanwhile, we're showing you how to manage small multiple plots in the Points of View column Unentangling Complex Plots.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of View column: Unentangling complex plots. (download, more about Points of View)

Data in small multiples can vary in range, noise level and trend. Gregor McInerny and myself show you how you can deal with this by cropped and scaling the multiples to a different range to emphasize relative changes while preserving the context of the full data range to show absolute changes.

McInerny, G. & Krzywinski, M. (2015) Points of View: Unentangling complex plots. Nature Methods 12:591.

...more about the Points of View column

Fixing Jurassic World science visualizations

Fri 10-07-2015

The Jurassic World Creation Lab webpage shows you how one might create a dinosaur from a sample of DNA. First extract, sequence, assemble and fill in the gaps in the DNA and then incubate in an egg and wait.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
We can't get dinosaur genomics right, but we can get it less wrong. (a) Corn genome used in Jurassic World Creation Lab website. Image is from the Science publication B73 Maize Genome: Complexity, Diversity, and Dynamics. Photo and composite by Universal Studios and Amblin Entertainment. (b) Random data on 8 chromosomes from chicken genome resized to triceratops genome size (3.2 Gb). Image by Martin Krzywinski. (c) Actual genome data for lizard genome, UCSC anoCar2.0, May 2010. Image by Martin Krzywinski. Triceratops outline in (b,c) from wikipedia.

With enough time, you'll grow your own brand new dinosaur. Or a stalk of corn ... with more teeth.

What went wrong? Let me explain.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Corn World: Teeth on the Cob.

Printing Genomes

Tue 07-07-2015

You've seen bound volumes of printouts of the human reference genome. But what if at the Genome Sciences Center we wanted to print everything we sequence today?

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Curiously, printing is 44 times as expensive as sequencing. (details)

Gene Volume Control

Thu 11-06-2015

I was commissioned by Scientific American to create an information graphic based on Figure 9 in the landmark Nature Integrative analysis of 111 reference human epigenomes paper.

The original figure details the relationships between more than 100 sequenced epigenomes and genetic traits, including disease like Crohn's and Alzheimer's. These relationships were shown as a heatmap in which the epigenome-trait cell depicted the P value associated with tissue-specific H3K4me1 epigenetic modification in regions of the genome associated with the trait.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Figure 9 from Integrative analysis of 111 reference human epigenomes (Nature (2015) 518 317–330). (details)

As much as I distrust network diagrams, in this case this was the right way to show the data. The network was meticulously laid out by hand to draw attention to the layered groups of diseases of traits.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Network diagram redesign of the heatmap for a select set of traits. Only relationships with –log P > 3.9 are displayed. Appears on Graphic Science page in June 2015 issue of Scientific American. (details)

This was my second information graphic for the Graphic Science page. Last year, I illustrated the extent of differences in the gene sequence of humans, Denisovans, chimps and gorillas.